Draw HOMO LUMO with psikit-2 #chemoinformatics

Yesterday I wrote a post about psikit function for HOMO LUMO drawing. And @fmkz__ gave me very suggestive comment.

He performed QM calculation about tetrazole and disclosed the its distribution of negative charge.

I had interested in his suggestion and I tried it. By using psikit, I calculated energy of acetic acid and 5-methyl-1H-tetrazole and got HOMO LUMO cube files from the results.

Results is below. At first HOMO and LUMO of acetic acid.

HOMO of acetic acid
LUMO of acetic acid

These results shows that carbonyl C=O has large MO and it means carbonyl is most reactive position of the acetic acid. And also LUMO around the alpha carbon is large. It indicates that the site is reactive with electrophile I think.

Next, let’s see result of tetrazole. Tetrazole is often used in medicinal chemistry as a bioisoster of carboxylic acid.

HOMO of tetrazole
LUMO of tetrazole

These results shows 3-N position has large MO compared to other nitrogen atoms. I think it indicates that 3-N position is more reactive than other nitrogen. And I found good example to explain the result in slide share. URL is below.

Page 21 of the slide shows example of 5-sub tetrazoles alkylation.
The page shows example of reaction between 5-Me-1H-tetrazole and trityl-Cl. And most of alkylation occurred at n-3 position.

Borrowed from slide share

It is very exciting for me because I could know that QM is very useful tool for reactivity prediction. The result motivates me to enhance of psikit. ;-)

Any suggestion and advices are highly appreciated.


Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

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